Method of reducing blood glucose

- Novo Nordisk A/S

The present invention relates to the use of compounds of the general formula ##STR1## for reducing blood glucose and/or inhibit the secretion, circulation or effect of insulin antagonizing peptides like CGRP or amylin. Hence the compound can be used in the treatment of insulin resistance related to NIDDM (non-insulin-dependent diabetes mellitus) or aging.

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Claims

1. A method for reducing blood glucose and/or inhibiting the activity of CGRP comprising administering to a patient a clinically effective amount of a compound of formula I ##STR4## wherein R.sup.1 and R.sup.2 independently are hydrogen, halogen, trifluoromethyl, C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy;

Y is >N--CH.sub.2 --, >CH--CH.sub.2 -- or >C.dbd.CH-- wherein only the underscored atom participates in the ring system;
X is --O--, --S--, CR.sup.7 R.sup.8, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--CH.sub.2 --, --CH.sub.2 --CH.dbd.CH--, --CH.sub.2 CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, NR.sup.9 (C.dbd.O)--, --O--CH.sub.2 --, --(C.dbd.O)-- or --(S.dbd.O)-- wherein R.sup.7, R.sup.8 and R.sup.9 independently are hydrogen or C.sub.1-6 -alkyl;
r is 1, 2, or 3;
m is 1 or 2;
n is 1 when m is 1 and n is 0 when m is 2;
R.sup.4 and R.sup.5 represents hydrogen or may--when m is 2--together represent a bond; and
R.sup.6 is OH or C.sub.1-8 -alkoxy; or

2. The method according to claim 1 wherein R.sup.1 and R.sup.2 independently are hydrogen, halogen, triflouromethyl or methoxy.

3. The method according to claim 1 wherein Y is >N--CH.sub.2.

4. The method according to claim 3 wherein X is --O--, --S--, --(CH.sub.2).sub.2 --, --(CH.sub.2).sub.3 --, --CH.dbd.CH--, --N(CH.sub.3)(C.dbd.O)--, --O--CH.sub.2 --, --(C.dbd.O)-- or --(S.dbd.O)--.

5. The method according to claim 1 wherein Y is >C.dbd.CH--.

6. The method according to claim 5 wherein X is --O--, --S--, --(CH.sub.2).sub.2 --, --(CH.sub.2).sub.3 --, --CH.dbd.CH--, --N(CH.sub.3)(C.dbd.O)--, --O--CH.sub.2 --, --(C.dbd.O)-- or --(S.dbd.O)--.

7. The method according to claim 1 wherein X is --O--, --S--, --(CH.sub.2).sub.2 --, --(CH.sub.2).sub.3 --, --CH.dbd.CH--, --N(CH.sub.3)(C.dbd.O)--, --O--CH.sub.2 --, --(C.dbd.O)-- or --(S.dbd.O)--.

8. The method according to claim 1 wherein R.sup.6 is OH.

9. The method according to claim 1 wherein m is 1.

10. The method according to claim 1 wherein m is 2.

12. The method according to claim 1 wherein the compound is in a form suitable for oral administration.

13. The method according to claim 1 wherein the compound is administered at a dose in a range from about 0.5 to 1000 mg/day.

16. The method according to claim 1 wherein the compound is

(R)-1-(3-(5-Oxo-10H-phenothiazin-10-yl)-1-propyl)-3-piperidinecarboxylic acid;
(R)-1-(3-(10H-Phenoxazin-10-yl)-1-propyl)-3-piperidinecarboxylic acid; or

17. The method according to claim 1 wherein the compound is (R)-1-(3-(9(H)-Oxo-10H-acridin-10-yl)-1-propyl)-3-piperidinecarboxylic acid or a pharmaceutically acceptable salt thereof.

19. The method according to claim 1 wherein the compound is 1-(3-(Thioxanthen-9-ylidene)-1-propyl)-3-piperidinecarboxylic acid or a pharmaceutically acceptable salt thereof.

Referenced Cited
U.S. Patent Documents
3177211 April 1965 Zenitz et al.
Foreign Patent Documents
WO 92/06954 April 1992 WOX
WO 92/16226 October 1992 WOX
WO 95/18793 July 1995 WOX
Patent History
Patent number: 5741791
Type: Grant
Filed: Dec 13, 1996
Date of Patent: Apr 21, 1998
Assignee: Novo Nordisk A/S (Bagsvaerd)
Inventor: Uffe Bang Olsen (Vallensbaek)
Primary Examiner: Marianne M. Cintins
Assistant Examiner: Dwayne C. Jones
Attorneys: Steve T. Zelson, Esq., Eliass J. Lambiris, Esq.
Application Number: 8/766,839
Classifications
Current U.S. Class: 514/212; Ring Nitrogen In The Polycyclo Ring System (514/323); Ring Sulfur In The Polycyclo Ring System (514/324)
International Classification: A01N 4346; A61K 3155;